Pretransplantation tumor necrosis factor-α production predicts acute rejection after liver transplantation

Abstract

Immunosuppressive therapy has many adverse effects in both the short and longer term. Tailoring immunosuppression might be possible if pretransplantation parameters predicted rejection. We investigated production of the proinflammatory cytokine, tumor necrosis factor-␣ (TNF-␣), and the anti-inflammatory cytokine, interleukin-10 (IL-10), pretransplantation to determine whether there is a relation with acute rejection. Peripheral-blood mononuclear cells were obtained from patients with chronic liver disease on the waiting list for orthotopic liver transplantation and healthy controls. Cells (0.5 ؋ 10 6 ) were stimulated with 200 ng of lipopolysaccharide. Preincubation for 30 minutes with tacrolimus, cyclosporine, and dexamethasone at concentrations of 10 and 100 ng was also performed. TNF-␣ and IL-10 levels were measured by enzyme-linked immunosorbent assay. Acute rejection was defined on clinical and histological grounds. Pretransplantation in vitro production of TNF-␣ significantly (P < .05) increased in the group of patients with acute rejection (n ‫؍‬ 9) compared with those who did not develop rejection (n ‫؍‬ 12). Preincubation with dexamethasone significantly (P < .001) reduced TNF-␣ and IL-10 production in both patients and controls (n ‫؍‬ 8). IL-10 production pretransplantation was not different in those who developed acute rejection (n ‫؍‬ 9) compared with those who did not (n ‫؍‬ 9). Preincubation with tacrolimus augmented (P < .05) the production of IL-10 in patients (n ‫؍‬ 18), but not controls (n ‫؍‬ 6). Pretransplantation TNF-␣ production is increased in patients who go on to develop acute rejection posttransplantion. (Liver Transpl 2000;6:721-727.)

Strain-specific in vitro cytokine production profiles do not predict rat liver allograft survival

“…In accordance with results from this animal study, human studies investigating pre-and post-transplant in vitro cytokine responses did not find an association between differential production of IL-10 and the occurrence of acute liver graft rejection [14,151. Since LEW and PVG did not differ in rejection grade and in vitro TNF-a responses, our results neither support nor contradict previous studies showing an association between higher in vitro production of TNF-a and the occurrence of acute human liver graft rejection [14, 151. In conclusion, different inbred rat strains could be classified as high-, intermediate-or low-responders with regard to in vitro TNF-a, IFN-y, IL-6 and IL-10 production since naive animals of different strains show differences in their capacity to produce cytokines upon a standardized in vitro stimulus.…”

“…Furthermore, some cytokine gene polymorphisms have been associated with the occurrence of human solid organ graft rejection [9, 10,11,12,131. More recently, differential levels of in vitro TNF-alpha production have also been associated with human liver allograft rejection [14,151. In vitro cytokiiie responses can be affected by factors such as age, underlying disease and immunosuppressive therapy [16,17,181.…”

Role of natural killer cells in liver transplantation treatment of liver cancer

“…Thus, depending on the cytokines that are present when antigen activation occurs, innate immune cells including macrophages, dendric cells and NK cells, may acquire cytopathic and/or immunoregulatory phenotypes. TNF-α is primarily produced by monocytes or macrophages, it has been demonstrated that pre-transplant in vitro production of this molecule was significantly increased in patients with post-transplant acute rejection compared with those who did not develop acute rejection (31)(32)(33)(34).…”

Correlation of CD95 and soluble CD95 expression with acute rejection status of liver transplantation

“…They control the activation and differentiation of immune effector cells and mediate cytotoxic activity of the effector cells. It has been suggested that Type I CD4 + and CD8 + T cells (Th1, Tc1) cytokines (interleukin-2, interferon- and tumor necrosis factor (TNF)-) might promote cellular rejection [1][2][3] , whereas type II CD4 + and CD8 + T cells (Th2, Tc2) cytokines (interleukin-4 and interleukin-10) might suppress graft rejection [4] . T cells stimulated via the T-cell receptors (TCRs) not only proliferate, but also undergo subsequent apoptosis by activation-induced cell death (AICD) [5,6] .…”